Di Paolo T, Bédard P, Daigle M, Boucher R
Brain Res. 1986 Aug 6;379(2):286-93. doi: 10.1016/0006-8993(86)90782-1.
5 Macaca fascicularis monkeys developed a severe parkinsonian syndrome in the days following intravenous administration of the toxin MPTP. One monkey remained untreated while two groups of two animals were treated daily for 5 months with supramaximal oral doses of either Sinemet or bromocriptine. Both drugs relieved the parkinsonian symptoms. Plasma prolactin concentrations were elevated in MPTP-treated monkeys compared to intact monkeys. MPTP caused a rapid decrease of homovanillic acid (HVA) concentrations in the CSF of these monkeys within days of the toxin injection and these values remained low until sacrifice of the animals 5 months later. By contrast, CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were elevated a few days after the start of MPTP treatment and these values returned to control levels by 5 months. Five months after the start of MPTP treatment, epinephrine (E) and dopamine (DA) levels were decreased in the adrenal medulla while the norepinephrine (NE) concentration remained unchanged. Catecholamines were assayed in the caudate putamen, nucleus accumbens, amygdala and frontal cortex of these monkeys. NE concentrations were decreased in the frontal cortex of MPTP-treated monkeys while a decrease of E concentrations after MPTP was only observed in the n. accumbens. Dopamine and its metabolites dihydroxyphenylacetic acid (DOPAC) and HVA were reduced in the caudate, putamen, n. accumbens and frontal cortex. Our results show that MPTP treatment in the long-term (5 months) not only affects the dopaminergic system of the caudate-putamen but also has effects on dopaminergic systems in other regions as well as on noradrenergic and adrenergic systems in the brain and the periphery.
5只食蟹猴在静脉注射毒素MPTP后的数天内出现了严重的帕金森综合征。1只猴子未接受治疗，而两组各2只动物每天接受超最大口服剂量的息宁或溴隐亭治疗，持续5个月。两种药物均缓解了帕金森症状。与未处理的猴子相比，MPTP处理的猴子血浆催乳素浓度升高。MPTP在毒素注射后的数天内使这些猴子脑脊液中的高香草酸（HVA）浓度迅速下降，这些值在动物被处死前5个月一直保持在低水平。相比之下，MPTP治疗开始几天后脑脊液5-羟吲哚乙酸（5-HIAA）浓度升高，这些值在5个月时恢复到对照水平。MPTP治疗开始5个月后，肾上腺髓质中的肾上腺素（E）和多巴胺（DA）水平下降，而去甲肾上腺素（NE）浓度保持不变。对这些猴子的尾状核壳核、伏隔核、杏仁核和额叶皮质中的儿茶酚胺进行了检测。MPTP处理的猴子额叶皮质中的NE浓度下降，而MPTP处理后E浓度的下降仅在伏隔核中观察到。尾状核、壳核、伏隔核和额叶皮质中的多巴胺及其代谢产物二羟基苯乙酸（DOPAC）和HVA减少。我们的结果表明，长期（5个月）MPTP处理不仅影响尾状核-壳核的多巴胺能系统，而且对其他区域的多巴胺能系统以及大脑和外周的去甲肾上腺素能和肾上腺素能系统也有影响。
